This research plan is a further continuation of our effort to clarify the biosynthetic mechanism by which porphebilinogen is transformed into uroporphyrinegens III and I which was started under Grant GM-11973. This biosynthetic mechanism is closely related to the congenital and acquired metabolic diseases known as porphyrias. In our previous work we developed synthetic methods for 2- aminomethyldipyrrylmethanes and 2-aminomethyltripyrpanes formally derived from porphobilinogen, as well as related 2-aminothypyrpoles. We intend to develop further the method to obtain the isomeric tripyopranes and 2-aminom thylbilanaes. The results of the specific enzymatic incorporations of the synthetic pyrmdmethanes into uroporphyringaens allowed to settle the nature of the rearrangement mechanism underlying the biosynthesis of uroporphyninogen III. The study of perphebilinogen oxygenase, as well as of skatole pyproloexygenase and of tryplophan pyrroloexygenase will allow to clarify a series of new control mechanisms in porphyrin biosynthesis and possibly also in other relevant metabolisms.